Since ancient times, cabbages and other extracts of the botanic family Brassicacea have been used as natural antibiotics and key components of antiviral drugs and antimycotics. Members of the Brassicacea family contain glycosides that trigger the release of mustard oils after enzymatical hydrolyzation, in case of physical damage of the plant cells. These mustard oils offer protection against microorganisms and fungi. To date, the bioactive function of more than 120 different mustard oils have been documented .
With regard to numerous worldwide studies, an inverse relationship between consumption of cruciferous vegetables (including members of the Brassicacea family) and the risk of neoplastic diseases has been observed, namely in colorectal, gastric, lung, breast, prostate, bladder, and endometrial cancers [18, 19]. The bioactive phytochemicals, sulforaphane and quercetin have been shown to be potent substances that possess chemopreventive and therapeutic properties beneficial in cancers of the intestine, breast [28, 29], prostate , and pancreas . Sulforaphane, and its inactive glycoside precursor, glucoraphanin, are present in high concentrations in broccoli and its sprouts [18, 19]. Sulforaphane is a potent antioxidant that indirectly eliminates free radicals; by increasing the concentration of glutathione, sulforaphane inhibits the formation and accumulation of carcinogen-induced DNA adducts [18, 36], a finding that has been demonstrated in several animal studies [25, 26]. Furthermore, sulforaphane is of interest as a new therapeutic anti-cancer substance, based on recent experimental studies in which the compound has been shown to target CSCs in models of pancreatic, breast, and prostate cancer [20, 21]. In pancreatic cancer, sulforaphane was shown to exhibit its anti-CSC effect through the downregulation of NF-κB activity, which is usually enhanced in active CSCs . Consequently, sulforaphane might be effective in overcoming the resistance of pancreatic cancer cells to chemotherapy, as underlined by recent experimental studies. These studies show that sulforaphane increases the responsiveness of pancreatic CSCs to sorafenib, gemcitabine, cisplatin, doxorubicin, and 5-fluorouracil [20, 22, 23].
Another bioactive agent is quercetin, a polyphenol flavonoid commonly found in apples, berries, red grapes, onions, and broccoli,  with antioxidant, anticarcinogenic, anti-inflammatory and cardioprotective activities [38, 39]. Recent reports describe the possible use of quercetin to inhibit the self-renewal and therapy resistance of pancreatic CSCs by affecting clonogenicity, spheroid formation, and aldehyde dehydrogenase isoform 1 (ALDH1) activity, as well as blocking the signaling pathways involved in apoptosis resistance, proliferation, angiogenesis, NF-κB activity, and epithelial-mesenchymal transition (EMT) . It is most effective in combination with sulforaphane both in vitro and in vivo, without inducing toxic side effects in mice . These findings emphasize the need for dietary intervention studies to elucidate the therapeutic effects of vegetables rich in sulforaphane and quercetin for more successful treatment of therapy-resistant PDA.
Since 2012 a pilot study has been evaluating the dose-dependent effects of broccoli sprout extract on atypical nevi, as precursor lesions and malignant melanoma (clinicaltials.gov identifier: NCT01568996) in an 18-patient collective. Two other ongoing pilot studies are examining the preoperative administration of broccoli sprout extract in patients with transitional cell bladder cancer undergoing surgery (NLM identifier: NCT01108003) and the additive intake of broccoli sprout extract in patients with recurrent prostate cancer (clinicaltrials.gov identifier: NCT01228084).
From the available studies, it can be noted that there is a positive correlation between the consumption of broccoli and an increased efficacy of chemotherapy [27, 40]. However, to date this is not based on high-level evidence trials. The POUDER trial will not interfere with any palliative chemotherapy or targeted therapy as these substances typically do not require any food restrictions. Consequently, patients who participate in PDA trials can simultaneously participate in a broccoli nutritional study. However, compounding effects of the intake of broccoli sprouts might have an influence on the results of any parallel trial due to the potential benefit of their application. The present trial has to be regarded as a test of feasibility. Participation in other treatment schemes - regardless of whether or not standard or study substances are applied - was not defined as a contraindication for inclusion. As patients suffering from tumor diseases are often encouraged to make healthy changes in their lifestyle, other phytotherapies may be expected. Yet, the effects of the chosen high dosage of the broccoli sprout extract will probably overpower the effects of any other nutritional substance.
A possible side effect of high broccoli sprout intake may be meteorism, which is a common phenomenon associated with cabbage consumption. Other effects include the prominence of the rotten-egg odor. During the metabolic breakdown of cabbage in the digestive tract, sulfur in the glucosinolates  is converted into the rotten-egg chemical, hydrogen sulfide, by gut bacteria. These potential side effects may be uncomfortable, but are considered to be insignificant in the overall context of a promising therapy for an advanced tumor disease.
With regard to sulforaphane, its modus operandi is believed to be as an indirect antioxidant that helps to protect healthy cells from oxidative damage and reduce the short- and long-term harmful effects of cancer treatment . However, concern has been raised that antioxidant supplements may also protect tumor cells during chemotherapy, thereby compromising treatment efficacy [42, 43]. This has resulted in controversy over the guidelines for the use of vitamin supplements during cancer treatment. This issue was examined in an experimental human PDA xenograft model in mice. In this setup, sulforaphane did not protect tumor cells; instead, it increased the effect of gemcitabine, cisplatin, doxorubicin, 5-fluorouracil, sorafenib, and TRAIL [20, 22, 23, 27].
In closing, the POUDER trial is the first clinical pilot trial to test the feasibility of an intake of freeze-dried broccoli sprouts as an additive of palliative chemotherapy in surgically non-resectable, advanced pancreatic cancer. Depending on the results of this pilot trial, a hypothesis for a confirmatory trial in the field will be generated and a consecutive RCT is planned.